大电导、电压和钙门控钾通道β(1)亚基的第二个跨膜结构域是石胆酸盐传感器。
The second transmembrane domain of the large conductance, voltage- and calcium-gated potassium channel beta(1) subunit is a lithocholate sensor.
作者信息
Bukiya Anna N, Vaithianathan Thirumalini, Toro Ligia, Dopico Alejandro M
机构信息
Department of Pharmacology, University of Tennessee HSC, Memphis, TN 38163, USA.
出版信息
FEBS Lett. 2008 Mar 5;582(5):673-8. doi: 10.1016/j.febslet.2008.01.036. Epub 2008 Jan 31.
Abstract
Bile acids and other steroids modify large conductance, calcium- and voltage-gated potassium (BK) channel activity contributing to non-genomic modulation of myogenic tone. Accessory BK beta(1) subunits are necessary for lithocholate (LC) to activate BK channels and vasodilate. The protein regions that sense steroid action, however, remain unknown. Using recombinant channels in 1-palmitoyl-2-oleoyl-phosphatidylethanolamine/1-palmitoyl-2-oleoyl-phosphatidylserine bilayers we now demonstrate that complex proteolipid domains and cytoarchitecture are unnecessary for beta(1) to mediate LC action; beta(1) and a simple phospholipid microenvironment suffice. Since beta(1) senses LC but beta(4) does not, we made chimeras swapping regions between these subunits and, following channel heterologous expression, demonstrate that beta(1) TM2 is a bile acid-recognizing sensor.
摘要
胆汁酸和其他类固醇可改变大电导、钙激活和电压门控钾（BK）通道活性，从而对肌源性张力进行非基因组调节。辅助性BK β(1)亚基是石胆酸（LC）激活BK通道并使其血管舒张所必需的。然而，感知类固醇作用的蛋白质区域仍不清楚。我们在1-棕榈酰-2-油酰-磷脂酰乙醇胺/1-棕榈酰-2-油酰-磷脂酰丝氨酸双层膜中使用重组通道，现在证明复杂的蛋白脂质结构域和细胞结构对于β(1)介导LC作用并非必需；β(1)和简单的磷脂微环境就足够了。由于β(1)能感知LC而β(4)不能，我们构建了在这些亚基之间交换区域的嵌合体，并在通道异源表达后证明β(1)的跨膜区2（TM2）是胆汁酸识别传感器。
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